Pesticidal phosphorylated thiazole derivatives

ABSTRACT

NOVEL PESTICIDAL PHOSPHORYLATED THIAZOLE DERIVATIVES.

United States Patent O 3 Claims ABSTRACT OF THE DISCLOSURE Novelpesticidal phosphorylated thiazole derivatives.

FIELD OF THE INVENTION This invention relates to the use as pesticidesof novel thiazole derivatives phosphorylated at the -posit1on of thering.

DESCRIPTION OF THE PRIOR ART A search has disclosed no phosphorylatedthiazoles of this invention or use of any such as pesticides.

PREFERRED EMBODIMENTS OF THE INVENTION The present invention providesthiazole derivatives of general formula:

wherein R is alkyl, alkoxy or phenyl; R is alkyl, alkylthio,alkylthioalkyl or phenyl; R is alkyl; R, is alkyl, alkoxy ordialkylamino.

Preferred thiazole derivatives are those of Formula I wherein Rrepresents an alkyl or alkoxy group of 1-6 carbon atoms, for examplemethyl, isopropyl or isoproxy, or a phenyl group; R represents an alkyl,alkylthio or alkylthioalkyl group of up to 6 carbon atoms, for examplemethyl, isopropyl, s-butyl, methylthio or methylthioethyl, or a phenylgroup; R represents an alkyl group of 1-6 carbon atoms, for examplemethyl or ethyl; and R represents an alkyl, alkoxy or dialkylamino groupof up to 6 carbon atoms, for example ethyl, methoxy, ethoxy ordimethylamino.

The thiazole derivatives are prepared by a process which comprisesreacting a thiazolone of formula:

Rt Rlxs -0 (I with a base and a phosphorus halide of formula:

i Hal 3,784,554 Patented Jan. 8, 1974 convenient method comprisesreacting a N-thioacyl amino acid derivatives of the formula withphosphorus tribromide and liberating the thiazolone by treating theresulting hydrobromide salt with a su table base, such as sodiumbicarbonate. This process is lllustrated in the following examples, theidentity of the product, in each case, being confirmed by elementalanalysis.

EXAMPLE I Preparation of 4-isopropyl-2-methylthio thiazol-S-one Valine(11.7 grams) was dissolved in water (30 milliliters) containingpotassium hydroxide (11.2 grams) and the solution was cooled to 10 C.Carbon disulphide (7.6 grams) was added to the solution and the mixturewas stirred for 5 hours. Methyl iodide (14.7 grams) was added to theorange solution which was then cooled and stirred for a further onehour. The solution was acidified with concentrated hydrochloric acid (10milliliters) and extracted with ether. The dried extracts wereevaporated to give a yellow syrup which solidified on standing. Thesolid was recrystallized from a benzene/petroleum ether mixture. Thepure intermediate (5.0 grams) was dissolved in benzene (50 milliliters)containing acetic anhydride (2.5 grams) and the solution was allowed tostand for 48 hours at C. The solution was then washed with aqueoussaturated sodium bicarbonate solution, dried and evaporated to leave thethiazolone as a yellow oil.

EXAMPLE II Preparation of 2-methyl-4-sec-butyl thiazol-S-oneN-thioacetylisoleucine (12.2 grams) was dissolved in tetrahydrofuran (50milliliters) and to this solution was added dropwise a solution ofphosphorous tribromide (18.5 grams) in tetrahydrofuran (25 milliliters).The white precipitate formed was filtered off, washed, dried andsuspended in dichloromethane (50 milliliters). Aqueous sodiumbicarbonate solution was added to the suspension until its pH reached 8.The organic layer was separated, dried over anhydrous magnesium sulfateand the solvent removed under reduced pressure to leave the thiazoloneas a pale yellow oil.

EXAMPLE III Preparation of 2-isopropoxy-4-isopropylthiazol-S-oneIsopropyl-(l carboxyisobutyl)thionocarbamate (15.5 grams) in drytetrahydrofuran (70 milliliters) was mixed with dicyclohexylcarbodiimide(15.5 grams) in tetrahydrofuran (70 milliliters) and the mixture wasallowed to stand for two hours at room temperature. The mixture was thenfiltered and the filtrate evaporated under reduced pressure. The residuewas taken up in ether and the solution filtered and evaporated to leavea brown oil which was purified by distillation to give the thiazolone asa colorless oil boiling point 60 C. at 0.7 torr.

Other thiazolone precursors were prepared and identified in a similarmanner.

As mentioned above the thiazole derivatives of the invention are ofinterest as pesticides, and in particular as broad spectrum insecticidesand acaricides having relatively low toxicity to mammals. The inventionincludes therefore pesticidal compositions comprising a carrier or asurface-active agent, or both a carrier and a surface-active agent, and,as active ingredient, at least one thiazole derivative of the invention.Likewise the invention includes also a method of combatting insect oracarid pests at a locus which comprises applying to the locus apesticidally eflective amount of a thiazole derivative or composition ofthe invention.

The term carrier as used herein means a solid or fluid material, whichmay be inorganic or organic and of synthetic or natural origin, withwhich the active compound is mixed or formulated to facilitate itsapplication to the plant, seed, soil or other object to be treated, orits storage, transport or handling.

The surface-active agent may be an emulsifying agent, a dispersing agentor a wetting agent, and may be ionic or non-ionic.

Any of the carrier materials or surface-active agents usually applied informulating pesticides may be used and suitable examples of these are tobe found, for example, in British Pat. No. 1,232,930.

The compositions of the invention may be formulated as wettable powders,dusts, granules, solutions, emulsifiable concentrates, emulsionssuspension concentrates and aerosols. Wettable powders are usuallycompounded to contain 25, 50 or 75% w. of toxicant and usually contain,in addition to solid carrier, 310% w. of a dispersing agent, and, wherenecessary, -10% W. of stabilizer(s) and/or other additives such aspenetrants or stickers. Dusts are usually formulated as a dustconcentrate having a similar composition to that of a wettable powderbut without a dispersant, and are diluted in the field with furthersolid carrier to give a composition usually containing /2*10% W. oftoxicant. Granules are usually prepared to have a size between 10 and100 BS mesh (1.6760.152 mm.), and may be manufactured by agglomerationor impregnation techniques. Generally, granules will contain /225% w.toxicant and 010% w. of additives such as stabilizers, slow releasemodifiers and binding agents. Emulsifiable concentrates usually contain,in addition to the solvent and, when necessary, co-solvent, l050% w./v.toxicant, 220% w./v. emulsifiers and 0-20% w./v. of appropriateadditives such as stabilizers, penetrants and corrosion inhibitors.Suspension concentrates are compounded so as to obtain a stable,non-sedimenting, flowable product and usually contain 1075% w. toxicant,05-15% w. of dispersing agents, 0.1-% of suspending agents such asprotective colloids and thixotropic agents, 0l0% w. of appropriateadditives such as defoamers, corrosion inhibitors, stabilizers,penetrants and stickers, and as carrier, water or an organic liquidin'which the toxicant is substantially insoluble; certain organic solidsor inorganic salts may be dissolved in the carrier to assist inpreventing sedimentation or as antifreeze agents for water.

The compositions of the invention may also contain other ingredients,for example, other compounds possessing pesticidal in particularinsecticidal, acaricidal, herbicidal, or fungicidal properties.

Aqueous dispersion and emulsions, for example, compositions obtained bydiluting a wettable powder or an emulsifiable concentrate according tothe invention with water, also lie within the scope of the presentinvention. The said emulsions may be of the water-in-oil or of theoil-in-water type, and may have a thick mayonnaise-like consistency.

The invention is further illustrated in the following examples, in whichthe identity of each of the compounds was confirmed by elementalanalysis and nuclear magnetic resonance spectrum.

EXAMPLE IV Dimethyl- (4-isopropyl-Z-phenylthiazol-5-yl)phosphorothionate 4-isopropyl-2-phenylthiazol-5-one (3.3 grams) wasdissolved in a 10% mixture of dimethyl formamide in dry benzene (100milliliters) and sodium hydride (0.36 gram) was added portionwise to thesolution. Dimethyl phosphorochloridothionate (2.4 grams) was then addedand the mixture was stirred for two hours at room temperature.

The mixture was then poured into water and the benzene layer separated.The aqueous layer was extracted with ether and the extracts combinedwith the benzene solution. The organic solution was dried and evaporatedunder reduced pressure. The residue was chromatographed on silica gelusing 5% acetone in petroleum ether as eluant to give the desiredproduct as an oil.

EXAMPLE V (4-isopropyl-2-methyl-1,3-thiazol-5-yl)-methyl-N,N- dimethylphosphoroamidothionate 4 isopropyl-Z-methylthiazolin-S-one (3.3 grams)was dissolved in dry tetrahydrofuran (50 milliliters) and the solutionwas cooled in an ice bath. Sodium hydride (0.48 gram) was added to thesolution, followed by methyl, N,N-dimethylphosphoroamidochloridothionate (3.4 grams) with stirring. Thestirring was continued for 2 hours after which the solvent was removedunder reduced pressure. The residue was dissolved in ether and thesolution was washed with water and dried with magnesium sulfate. Theether was removed under reduced pressure and the pale yellow oilobtained was purified by chromatography on silica gel using a 10.1hexane/acetone mixture as eluant to give the desired product as an oil.

EXAMPLE VI Following procedures similar to that given in these examples,the following further species were prepared:

dimethyl- (4-is opropyl-2-methylthiazol-S-yl )phosphorothionatedimethyl- 4- 2-methylthioethyl) -2-phenylthiazol-5-yl) phosphorothionatedimethyl- (2,4-diphenylthiazolw5-yl phosphorothionate dimethyl-2-methyl-4-methylthiothiazol-S-yl phosphorothionate dimethyl-2,4-diisopropylthiazol-5-yl phosphorothionate dimethyl-(2-isopropyl-4-s-butyl-thiazol-S-yl phosphorothionate dimethyl-(2-methyl-4-s-b utylthiazol-S-yl phosphorothionateO-methyl-O-(4-isopropyl-2-methylthiazol-5-yl ethylphosphonothionatedimethyl- (2-isopropoxy-4-isopropylthiazol-S-yl phosphorothionatediethyl- (4-isopropyl-Z-phenylthiazol-5-yl) phosphorothionate ethyl-(4-isopropyl-2-phenylthiazol-S-yl methylphosphorothionate O-methyl-O-(4-isopropyl-2-phenylthiazol-S-yl) ethylphosphonothionate dimethyl-(4-methyl-2-phenylthiazol-S-yl phosphorothionate diethyl-(4-methyl-2-phenylthiazol-5-yl phosphorothionate.

EXAMPLE VII Insecticidal and acaricidal activity The insecticidal andacaricidal activity of compounds of the invention was tested as follows:

(I) A 0.1% by weight solution in acetone of the compound to be testedwas prepared, and taken up in a micrometer syringe. Two to three-day oldadult female houseflies (Musca domestica) were anaesthetized with carbondioxide, and a 1 microliter drop of the test solution was brushed off onthe ventral abdomen of each, 20 flies being treated. The treated flieswere held for 24 hours in glass jars, each containing a littlegranulated sugar as food for the flies, and the percentage of dead andmoribund individuals was then recorded.

(II) A quantity of 0.1 milliliter of a 0.1% by weight solution of thecompound to be tested in acetone was mixed in a beaker with millilitersof water. Twenty 5-6 day old (4th instar) mosquito larvae (Aedesaegypti) were added and the beakers stored for 24 hours. The

6 A denotes total kill, B some kill and C no kill of the test species.

TABLE 1 N-'-R1 S OH:

11/ B1 8 O-P\ Compound Activity M. domes- P. coch- P. macu- P. brus- M.013- T. ur- R1 R1 R3 R tica A. aeyyp i Zean'ae lipennis atone ciae timeOH; 011mm), OH; OCH: A A A A A A A 09H, 0116311,), OH; 0011a A A A A A BA 05H; CHZCHQSCH HI OCH: A A (3 G B Cells CaHs Ha OCHs C A C O C B (His8011:: Ha OCH: A A B A A A A (011,).03 011mm): 0H3 0011: A A A A A A ACHs :CH CH onooim OH OCH; A A A A A A A CH: CH CHDCgHs CH3 OCHa A A A AA A. CH1 H CH3) CH3 02H; A B A A A A A (CHshCHO CH GHs): OH: OCH: A A AA A A A 0.11, H CHa): 02H; 002E A A B B A A A GQH; CH OHa): OH; 00111; AA A A A B A 09H; CH CH3), CH9 CzHs A A A A A A. A 0.115 CH CH8 OCH: A AA A A A A can OH: 02H. 001m A A A A A A A percentage of dead andmoribund larvae was then re- I claim as my invention:

corded. 1. A thiazole derivative of the general formula.

(III) The compounds were formulated as solutions or suspension in watercontaining 20% by weight of acetone N- R, 8 OR and 0.05% by weight ofTriton X-100 as wetting agent. I l H The formulations contained 0.2% byweight of the com- R1 0-P 8 pound to be tested. Turmp and broad beanplants, R

trimmed to one leaf each, were sprayed on the under surface of the leafwith the above formulation. Spraying was effected with a sprayingmachine delivering 450 liters per hectare, the plants passing under thespray on a moving belt. Ten 4th instar (8 day old) diamond-back mothlarvae (Plutella maculipennz's) or ten adult 12 week old mustard beetles(Phaeaon cochleariae) were placed on the sprayed leaf of each turnipplant and ten apterous (6 day old) vetch aphids (Megoura viciae) wereplaced on the sprayed leaf of each broad bean plant. The plants werethen enclosed in glass cylinders fitted at one end with a muslin cap.Mortality counts were made after 24 hours.

(IV) In tests against glass house spider mites (Tetranychus urticae)leaf discs cut from French bean plants were sprayed in the mannerdescribed under (HI). One hour after spraying, the discs were inoculatedwith 10 adult mites. Mortality counts were made 24 hours afterinoculation.

(V) In tests against large white butterfly larvae (Pieris brassicae),leaf discs cut from cabbage leaves were sprayed in the manner describedunder (IH). 10 3rd instar (8-10 day old) larvae were placed on the discswithin petri-dish pairs. Mortality counts were made 24 hours afterinoculation.

The results of these tests are set out in Table I in which wherein R isalkyl or alkoxy of 1-6 carbon atoms, or phenyl; R is alkyl, alkylthio oralkylthioalkyl of up to 6 carbon atoms, or phenyl; R is alkyl of 1-6carbon atoms; and R is alkyl, alkoxy, or dialkylamino of up to 6 carbonatoms.

2. A thiazole derivative as claimed in claim 1 wherein R represents analkyl group of 1-6 carbon atoms or a phenyl group; and R represents analkoxy group of 1-6 carbon atoms.

3. A thiazole derivative as claimed in claim 2 wherein R is methyl,isopropyl, isopropoxy or phenyl; R is methyl, isopropyl, s-butyl,methylthio, methylthioethyl or phenyl; R is methyl or ethyl; and R isethyl, methoxy, ethoxy or dimethylamino.

References Cited UNITED STATES PATENTS 3,159,645 12/1964 Rigterink260-302 G RICHARD J. GALLAGHER, Primary Examiner US. Cl. X.R.

